Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Reexamination Certificate
1999-04-19
2002-10-01
Myers, Carla J. (Department: 1634)
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
C435S091200, C435S021000, C435S471000, C435S455000, C435S196000, C435S325000, C435S252300, C435S320100, C536S023100, C536S023500, C536S023200, C536S024310, C536S024330, C514S04400A
Reexamination Certificate
active
06458532
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to compositions and methods for determining the genotype associated with an increased or decreased susceptibility to manic-depressive illness. The invention also provides a means to determine an individual's increased or decreased risk of developing manic-depressive illness.
BACKGROUND OF THE INVENTION
Genome screening efforts by several groups, designed to identify regions linked to bipolar disorder, have revealed evidence for potential susceptibility loci on chromosome 18. Berrettini (1994)
Proc Natl Acad Sci USA
91:5918-5921, reported evidence for a susceptibility locus in the pericentromeric region of the chromosome. In a subsequent study on an independent pedigree series, Stine (1995)
Am. J. Hum. Genet
. 57:1384-1394, found support for the prior hypothesis on 18p (Berrettini et al.,
Proc Natl Acad. Sci. USA
, 91:5918-5921, 1994). In the same study, Stine (1995) supra, presented evidence for a possible additional linkage on 18q. Recently, Freimer (1996)
Nature Genet
. 12:436-441, proposed a predisposing locus close to the telomere of 18q in Costa Rican kindreds. These reports suggest that the regions potentially implicated in bipolar disorder encompass a very large portion of chromosome 18.
In addition to bipolar disorder, more than 25 other diseases have been localized to chromosome 18, approximately 80% of which still await the discovery of the underlying defective gene (Overhauser et al.,
Cytogenet Cell Gene
, 71:106-117, 1995; Online Mendelian Inheritance in Man (OMIM) (TM). (Database on line. 1995; URL: http://www3.ncbi.nlm.nih.gov/omim/. cited Jan. 19, 1996)). Since this chromosome has a genetic length estimated to be 150 cM [Cooperative Human Linkage Center (CHLC),
Science
265:2049-2054, 1994], which includes about 4.5% of the total length of the genome, it is expected to encode several thousand genes. Approximately 40 genes have been mapped to this chromosome [Overhauser et al., 1995; Genome Database (GDB), URL: http.//gdbwww.gdb.org/gdb/browser/docs/topq.html>[database online]. (1990-). Updated daily (cited Jan. 19, 1996]; OMIM, [Database on line. 1995; cited Jan. 19, 1996]. Between 1993 and 1995, only 14 genes have been added to the list of chromosome 18 genes (Geurts van Kessel et al.,
Cytogenet Cell Gene
, 65:141-165, 1994; Overhauser et al.,
Cytogenet Cell Gene
, 71:106-117, 1995). Therefore, a dense transcriptional map, which would be valuable in positional cloning of susceptibility genes, remains to be developed for chromosome 18.
SUMMARY OF THE INVENTION
In one aspect the present invention is directed to a method for determining a genotype associated with increased susceptibility to manic-depressive illness. The method comprises determining the genotype of an affected individual with at least one polymorphic marker localized within the chromosomal region defined by and including markers D18S843 and D18S869, and determining therefrom the genotype associated with increased susceptibility to manic-depressive disorder.
In preferred embodiments the polymorphic marker is amplified by primers which selectively hybridize, under stringent conditions, to the same nucleic acid sequences as primers of SEQ ID NO:1 and SEQ ID NO:2 (see Table 1, below, forward and reverse primers to amplify Clone 22). Typically the polymorphic marker is amplified by the polymerase chain reaction.
In other embodiments the method of further comprises determining the genotype of a tested individual wherein the genotype is determined with at least one polymorphic marker localized within the chromosomal region defined by and including markers D18S843 and D18S869. The genotype of the tested individual is compared to the genotype associated with increased susceptibility to manic-depressive illness and the increased or decreased risk of the tested individual developing manic-depressive illness is
TABLE 1
PCR PRIMER SEQUENCES
SEQ
SEQ
Name
Primers
ID NO:
Name
Primers
ID NO:
Clone 22
F-TACAAAAGAGGACAAAGCAC
30
D18S73
F-TGCCACTGCAACAATGC
31
R-GGTGCCTGTATATAAGTTGA
32
R-CCCAGCAATCAACCTTTAAG
33
Clone 24
F-CTACAGAATAGAATACATGGCG
34
D18S869
F-TGTTTATTTGTTTGACTCAATGG
35
R-GAGCTCTGAACTGTATTCAGA
36
R-GAGTGAATGCTGTACAAACAGC
37
Clone 29
F-TCTCAGCTTACTCAACCT
38
D18S996
F-GATGGAAAGCCATTTTATTTTTC
39
R-GATGAGGTGGAACAATCAC
40
R-TCGTACTATGAAATTTTTAAGCCTT
41
GNAL
F-GGTCTGTACAGTGTAATAAACC
42
FB14A10
F-CCTTCCCCTCTATTCTCAAA
43
R-CTACTGCAAAATGTGTCCTGTC
44
R-GAGCGAGACTGTCTCAAAAA
45
Clone 37
F-CACATTAGCCAGTCTGATAAAG
46
GC32001
F-GAGTTGTGGGGGGGAATAGT
47
R-AAGTTACACACAGTAGCTGA
48
R-ATACGGAGGTTGAACTAGGAAGG
49
AFMa058yg5
F-TAGATGCTATATTAGGCTGGGTCTC
50
GP4B15
F-CGGTTCTGGATTTATCAGTA
51
R-GAACTTACAGCACTGGCTCTCC
52
R-AGGGTTGCAATGAGCTGAG
53
AFMa152wg9
F-AAGAACAAAAGGTCACCTGTCA
54
IB-1114
F-GCCACACACAAATTTTTCTC
55
R-TGTCTCACCTCTGCTCACTCAT
56
R-ACAGGGTGTAAGAGGAGAGG
57
CHLC.GGA16G02
F-ATGGAAGGAAAAACAGAGGG
58
NIB-1802
F-CTGATCACATTTCATACAGC
59
R-GAACTCTTCAAGAGGGGAGC
60
R-TGTATGTGGGCTTAACTGTT
61
D18S1114
F-ATCAGTATAATGATGGATGAATCAC
62
SGC-31363
F-CTACTGGGAGGTAGGTAATCTCAG
63
R-TGAGGCAAGAGGGTCAC
64
R-GCAAAACCAACCACATCAAA
65
D18S1116
F-TCTGCCACTTTTTATGGG
66
SGC34207
F-GATCCTGTTCTTTCAGCAGG
67
R-CAATGTTTTAACTTCTAGGACAAAT
68
R-TTTAACCAGCTGGAGTGAAGG
69
D18S1150
F-GGCACAGGAAACGTGAAT
70
WI-11680
F-ACAGATACTTTTCCACGCAACA
71
R-CACAAGGATGCCAGCC
72
R-AAAAAGATGTACGGTCTGGCC
73
D18S1153
F-ATGGAGGCTCTGAGACCCTT
74
WI-13171
F-TTTTATTTGGACAAGAGAACTTGTG
75
R-CTTGCCTGATGCCTGAAAT
76
R-ATGATCAGCTCTGAGGTGCA
77
D18S1158
F-GCATCTATGCAGTGCCAAAT
78
WI-18080
F-TGGCATAAAGTTTGCAAATATCA
79
R-TCATTAGCAACAAGGATCTCC
80
R-ATACACCAAAGGAGAAGGATTAACA
81
D18S1228
F-AGACAGTTGAAAAGGACACAAATG
82
D18S1066
F-TGCTGTTGCCTCTCAGCATCTC
83
R-TGGTGATGGGACTTTTCAAA
84
R-CACCTTTCAAGTGCTTGGCAGTC
85
D18S378
F-AGCCTGGGTGACAGAGCAA
86
D18S1215
F-GTTTGCTGCATCTCCCAATT
87
R-ACAGGGAAAGCTGGGGGAT
88
R-GTGCCCACATTGTTGTGAAG
89
D18S40
F-CAAGATAGATGCATTTTCCAGT
90
D18S1299
F-TTTAAGCCTCAAGGGACCCT
91
R-CATCCAAAGGGTGAATGTGT
92
R-AGATTGAGGACCAGGTGGTG
93
D18S464
F-GCCAGACTTTGTGCCATTTC
94
D18S1226
F-CTCTTAAGTTGAGTGAAGTGGAAGC
95
R-TTTCCTGAATCTCTTGTGGTTTG
96
R-CGCAAAAGTCAGGAAAGAGG
97
D18S482
F-ATGAGTGAATGCCAACTTCG
98
SHGC-32282
F-TTACGCATTTTGTATCAGACTTACA
99
R-CCTGGCTGACAGAGTGAGT
100
R-GGTGGAGTATCAGAAGTGATTTTAG
101
D18S53
F-GGTCACCTACAACTTTGGATG
102
D18S1315
F-TGGACTTCTACCCCCATCTG
103
R-TGCATGTAAATATCAGAGTCTGTT
104
R-TTTGAAACCTGGACACTTTGG
105
D18S71
F-ACCCGCTCAAAAGCCT
106
D18S843
F-GTCCTCATCTGTAAAACGGG
107
R-TTAATGGATTATCAAGAGTGGTTCT
108
R-CCACTAACTAGTTTGTGACTTTGG
109
determined therefrom. Generally, the polymorphic marker of the tested individual is amplified by primers which selectively hybridize, under stringent conditions, to the same nucleic acid sequences as primers of SEQ ID NO:1 and SEQ ID NO:2.
In another aspect, the present invention is directed to a nucleic acid composition comprising oligonucleotide primers which selectively hybridize, under stringent conditions, to the same nucleic acid sequence as primers of SEQ ID NO:1 and SEQ ID NO:2. In an additional aspect the present invention is directed to a nucleic acid of less than 10 kB and comprising a polymorphic marker amplified by oligonucleotide primers of SEQ ID NO:1 and SEQ ID NO:2.
In yet another aspect, the present invention is directed to a method for determining an increased susceptibility to manic-depressive illness in an individual, comprising determining the genotype of the individual with oligonucleotide primers. The oligonucleotide primers amplify a polymorphic site as primers of SEQ ID NO:1 and SEQ ID NO:2. This polymorphic marker can be found in at least two forms, designated as “allele 1” of clone 22 (SEQ ID NO:14) or “allele 2” of clone 22 (SEQ ID NO:15). The presence of allele 2 of the polymorphic marker indicates an increased susceptibility to manic-depressive illness.
The invention further provides for a isolated nucleic acid encoding an IMP.18p myo-inositol monophosphatase, the protein defined as having a calculated molecular weight of between about 22 to 34 kDa, and where the protein's activity includes hydrolysis of myo
Detera-Wadleigh Sevilla D.
Esterling Lisa E.
Sanders Alan R.
Yoshikawa Takeo
Myers Carla J.
The United States of America as represented by the Secretary of
Townsend and Townsend / and Crew LLP
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